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Česká republika Praha
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0032 (0)16 41 44 07
Recombinant human Interleukin-15 (IL15)
(Cat. No.: C016)
Interleukin-15 (IL-15) is a cytokine that possesses a variety of biological functions, including stimulation and maintenance of cellular immune responses. IL-15 stimulates the proliferation of T-lymphocytes, which requires interaction of IL-15 with components of IL-2R, including IL-2R and probably IL-2R gamma, but not IL-2R.
Recombinant Human IL-15 produced in E. coli is a single, non-glycosylated polypeptide chain containing 114 amino acids and having a molecular mass of 12774 Dalton.
Biological Activity: The ED50 as determined by the dose-dependant stimulation of the proliferation of CTLL-2 was found to be < 0.5 ng/ml, corresponding to a Specific Activity of 2.0 x 106 IU/mg.
Purity: Greater than 98.0% as determined by:
(a) Analysis by RP-HPLC.
(b) Anion-exchange FPLC.
(c) Analysis by reducing and non-reducing SDS-PAGE Silver Stained gel.
Amino-Acid Sequence: The sequence of the first five N-terminal amino acids was determined and was found to be Asn-Trp-Val-Asn-Val.
Endotoxin: Less than 0.1 ng/µg (IEU/µg) of rHuIL-15.
Formulation: The protein was lyophilized from a concentrated (1mg/ml) solution with 5mM Tris pH 8.0.
Storage: Lyophilized rHuIL-15 although stable at room temperature for 3 weeks, should be stored desiccated below -18oC. Upon reconstitution rHuIL-15 should be stored at 4oC between 2-7 days and for future use below -18oC. For long-term storage it is recommended to add a carrier protein (0.1% HSA or BSA).
Please avoid freeze-thaw cycles.
Reconstitution: It is recommended to reconstitute the lyophilized rHuIL-15 in sterile 18MΩ-cm H2O not less than 100µg/ml, which can then be further diluted to other aqueous solutions.
1: J Immunol 2009 Feb;Vol 182(3)
Increased IL-15 Production Is Associated with Higher Susceptibility of Memory CD4 T Cells to Simian Immunodeficiency Virus during Acute Infection.
[Abstract] Acute SIV infection is characterized by explosive infection of memory CD4 T cells in peripheral and mucosal tissues. Interestingly, relatively few memory CD4 T cells are infected until as late as days 7-8 after challenge. However, by day 10 postinfection, most of the memory CD4 T cells are infected and carry viral DNA. The rapidity with which infection expands within 2-3 days to encompass virtually the entire memory CD4 T cell compartment suggests significant alterations in the susceptibility of memory CD4 T cells to infection during this period. The mechanism(s) underlying this increased permissiveness to infection is not known. In this study, we show that IL-15 secretion significantly correlates with the up-regulated expression of CD4 on memory CD4 T cells
that is associated with increased permissiveness to SIV infection. Activation and proliferation of memory CD8, but not memory CD4 T cells, preceded the amplification of viral infection. Although memory CD4 T cells did not express normal activation markers, they displayed a significant up-regulation in the density of CD4 but not CCR5 expression between days 7 and 10 postinfection that correlated with increased plasma IL-15 levels and infection in these cells. Culture of purified CD4 T cells with IL-15 and/or SIV was associated with a significant increase in the expression of CD4 and infection of these sorted cells. Our results demonstrate that IL-15 contributes to the increased susceptibility of memory CD4 T cells to SIV during the early phase of acute SIV infection.
2: Curr HIV Res 2009 Jan;Vol 7(1)
IL-2, IL-7 and IL-15 as Immuno-Modulators During SIV/HIV Vaccination and Treatment.
[Abstract] While highly active antiretroviral therapy (HAART) regimens have proven to be effective in controlling active HIV replication, complete recovery of CD4+ T cells does not always occur, even among patients with high level virologic control. Recent advances in understanding the biology of T cell production and homeostasis have created the potential to augment anti-viral therapies with immunotherapies designed to facilitate recovery of the HIV-damaged immune system, in particular, the recovery of CD4+ T cell populations. The common gamma-chain cytokines IL-2, IL-7 and IL-15 are primary regulators of T cell homeostasis and thus have been considered prime candidate immunotherapeutics, both for increasing T cell levels/function and for augmenting vaccine-elicited
viral-specific T cell responses. Recent studies have established that these cytokines have distinct functional roles in immune homeostasis, which focus on specific T cell populations. The ability of these cytokines to provide immunotherapeutic benefit to HIV+ patients will depend on their ability to stably increase or functionally enhance the desired T cell target population without adverse virologic or clinical consequences.
3: Alcohol Clin Exp Res 2008 Dec;
Exogenous IL-15 in Combination With IL-15Ralpha Rescues Natural Killer Cells From Apoptosis Induced by Chronic Alcohol Consumption.
[Abstract] Background: Chronic alcohol consumption reduces the percentage and number of peripheral natural killer (NK) cells in mice and in humans. The underlying mechanism for these changes is only partly known. We recently found that chronic alcohol consumption inhibits NK cell release from the bone marrow (BM) and that this is associated with a decrease in splenic NK cells. The number of peripheral NK cells is tightly controlled by homeostatic proliferation. It is not known whether this mechanism is initiated in response to the reduction in splenic NK cells, or if so, why the steady state levels of NK cells are not restored. Methods: To examine this mechanism, female C57BL/6 mice were given 20% w/v alcohol in the drinking water for 3 months. NK cell proliferation and
apoptosis were determined before and after treatment with IL-15 alone or combined with its alpha receptor. Results: Chronic alcohol consumption invoked homeostatic proliferation of splenic NK cells in an attempt to return NK cells to normal levels; however, this did not happen due to enhanced apoptosis of NK cells relative to proliferation. Chronic alcohol consumption decreased IL-15 producing cells in the spleen but not in the BM. The numbers of NK cells in the alcohol-consuming mice returned to normal levels in the spleen and were higher than normal in the BM after 2 daily injections of IL-15; however, the enhanced rate of apoptosis due to alcohol consumption was not decreased in the spleen or BM. Combined IL-15 and IL-15Ralpha treatment decreased apoptosis of NK cells from
alcohol-consuming mice to levels similar to untreated water-drinking mice and greatly increased the percentage and number of NK cells in both the spleen and BM. Conclusion: Chronic alcohol consumption causes a self-unrecoverable loss of NK cells in the spleen by compromising NK cell release from the BM and enhancing splenic NK cell apoptosis that can be reversed with IL-15/IL-15Ralpha treatment.
4: Zhonghua Xue Ye Xue Za Zhi 2008
[Experimental study on IL-2- and IL-15 application in allogeneic hematopoietic stem cell transplantation]
[Abstract] OBJECTIVE: To explore the impact of IL-2- and IL-15-activated donor natural killer (NK) cell infusion on graft-versus-host-disease (GVHD) and graft-versus-leukemia (GVL) effect post allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The C57BL/6 mice splenic NK cells were selected by microbeads, and then expanded in the media containing IL-2 and IL-15. The killing activity of NK cells was detected. In the leukemia mouse model, recipients (BALB/c) were intraveneously inoculated with EL9611 leukemia cells 8 days before transplantation. Lethally irradiated BALB/c recipient mice were transplanted with 5 x 10(6) bone marrow cells (BMCs), or 5 x 10(6) BMCs plus 1 x 10(7) splenocyes with or without 1 x 10(7) activated NK cells. Additionally, NK
cell infusion group mice were intraperitoneally injected with a mixture of IL-2 and IL-15 post transplant. Survival time, GVHD occurrence, lineage chimerism, TRBV spectra-typing were observed post transplant. RESULTS: The purity of isolated splenic NK cells was 95.7% - 97.1%. The killing activity of NK cells after activation was increased by 3 times. GVHD did not occurred in allogeneic BMCs infusion group, whereas did from 1 week after transplant in allogeneic BMCs + splenocytes infusion group. The severity of GVHD in total body irradiation (TBI) experimental group was significantly lower than in splenocytes infusion group (P < 0.05). The survival time was 9.5 - 14.0 d in TBI alone coditioning group. In leukemia mouse model, 100 day survival rate was 10% the rest of them were died of
leukemia while in experimental group, the more than 100 days survival rate was 80% (P < 0.01). PB NK cells at 2 week post-transplant were 4.8% in experimental group and 2.8% in cotrol group. NK cells recovery in experimental group was earlier than that in control group (P < 0.05). TRBV reconstitution was faster in experimental group than in control group, moreover, the number of TRBV family expression was more in experimental group than in control group which mainly expressed monoclone or oligoclone. CONCLUSIONS: Donor alloreactive NK cells can be efficiently expanded and activated with IL-2 and IL-15. Donor activated NK cell infusion and IL-2, IL-15 treatment can promote immune reconstitution, mitigate GVHD and reduce leukemia relapse.
Protein Accession No.:
NWVNV ISDLK KIEDL IQSMH IDATL YTESD VHPSC KVTAM KCFLL ELQVI SLESG DASIH DTVEN LIILA NNSLS SNGNV TESGC KECEE LEEKN IKEFL QSFVH IVQMF INTS
*NOTE: ALL PRODUCTS ARE FOR RESEARCH USE ONLY